Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients

Objective To evaluate the prophylactic use of enteral fluconazole to preven t invasive candidal infections in critically ill surgical patients. Summary Background Data Invasive fungal infections are increasingly common in the critically ill, especially in surgical patients. Although fungal pro phylaxis has been proven effective in certain high-risk patients such as bo ne marrow transplant patients, few studies have focused on surgical patient s and prevention of fungal infection. Methods The authors conducted a prospective, randomized, placebo-controlled trial in a single-center, tertiary care surgical intensive care unit (ICU) . A total of 260 critically ill surgical patients with a length of ICU stay of at least 3 days were randomly assigned to receive either enteral flucon azole 400 mg or placebo per day during their stay in the surgical ICU at Jo hns Hopkins Hospital. Results The primary end point was the time to occurrence of fungal infectio n during the surgical ICU stay, with planned secondary analysis of patients "on-therapy" and alternate definitions of fungal infections. In a time-to- event analysis, the risk of candidal infection in patients receiving flucon azole was significantly less than the risk in patients receiving placebo. A fter adjusting for potentially confounding effects of the Acute Physiology and Chronic Health Evaluation (APACHE) III score, days to first dose, and f ungal colonization at enrollment, the risk of fungal infection was reduced by 55% in the fluconazole group. No difference in death rate was observed b etween patients receiving fluconazole and those receiving placebo. Conclusions Enteral fluconazole safely and effectively decreased the incide nce of fungal infections in high-risk, critically ill surgical patients.